Methods for the isolation of intact RNA from the cytoplasm of normal peripheral blood lymphocytes and lymphoblastoid cells have been developed. The procedures make use of ribonucleoside-vanadyl complexes as nuclease inhibitors during cell lysis and during subsequent purification of cytoplasmic particles on sucrose density gradients. Messenger RNA prepared from resting lymphocytes using these methods has a sedimentation value of 16S whether or not it is polysome-bound. The mRNA from normal cells is potentially capable of directing protein synthesis. Messenger RNA obtained from Namalva cells using these techniques is also translatable. After induction with virus a 13S mRNA was recovered from denaturing sucrose gradients which, when injected into frog oocytes, directed the synthesis of biologically active interferon.